V-H GENE USAGE IN MULTIPLE-MYELOMA - COMPLETE ABSENCE OF THE V(H)4.21(V(H)4-34) GENE

The immunoglobulin heavy chain variable region (V-H) gene usage in mul tiple myeloma (MM) has not been reported, although a few studies have incidentally identified the V-H gene rearranged in small cohorts of MM patients. We used a reverse trancriptase-polymerase chain reaction ba sed technique to analyze the V-H gene usage in MM. The V-H sequences w ere obtained after amplification of bone marrow cDNA using the seven V -H family-specific and constant region primers. The V-H sequences of 7 2 patients were successfully identified. The frequency of V-H family u sage in decreasing order was V(H)3 >V(H)4 >V(H)1 >V(H)5 >V(H)2 >V(H)6 >V(H)7 and corresponded to the functional germline complexity of the V -H families. Individual V-H genes (V(H)1-69, V(H)3-9, V(H)3-23, and V( H)3-30) were overrepresented in our cohort of MM patients; some V-H ge nes [V(H)3-49, V(H)3-53, and V(H)4.21 (V(H)4-34)], which are rearrange d with increased frequency in normal circulating B cells, autoimmune d iseases, and other B-cell malignancies, were not detected in any MM pa tient. Compared with germline sequences, an average of 8.8% (range, 2. 7% to 16.5%) of the nucleotides had evidence of mutation within each V H sequence. Based on these results, we conclude that (1) the V-H gene usage in MM is unique compared with other malignant and nonmalignant B -cell populations, (2) the physiologic process of clonal deletion func tions to remove clones that have rearranged V-H genes (V(H)4.21) capab le of expressing antibodies, which recognize self-antigens, and (3) th e complete lack of V(H)4.21 gene rearrangement may help to partially e xplain the paucity of autoimmune phenomena in MM. (C) 1996 by The Amer ican Society of Hematology.